EP0597167B1 - Veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding - Google Patents
Veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding Download PDFInfo
- Publication number
- EP0597167B1 EP0597167B1 EP93100071A EP93100071A EP0597167B1 EP 0597167 B1 EP0597167 B1 EP 0597167B1 EP 93100071 A EP93100071 A EP 93100071A EP 93100071 A EP93100071 A EP 93100071A EP 0597167 B1 EP0597167 B1 EP 0597167B1
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- European Patent Office
- Prior art keywords
- pigs
- composition
- drinking water
- lincomycin
- animal feed
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- Expired - Lifetime
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- 241001465754 Metazoa Species 0.000 title claims abstract description 42
- 239000003651 drinking water Substances 0.000 title claims abstract description 26
- 235000020188 drinking water Nutrition 0.000 title claims abstract description 26
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 229960005287 lincomycin Drugs 0.000 title claims abstract description 15
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 title claims abstract description 15
- 229930182566 Gentamicin Natural products 0.000 title claims abstract description 14
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 title claims abstract description 13
- 229960002518 gentamicin Drugs 0.000 title claims abstract description 13
- 239000000203 mixture Substances 0.000 title claims description 62
- 239000003242 anti bacterial agent Substances 0.000 title claims description 33
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- 239000002253 acid Substances 0.000 claims abstract description 5
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 claims description 8
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical compound Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 claims description 8
- 229960001595 lincomycin hydrochloride Drugs 0.000 claims description 8
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- 208000024891 symptom Diseases 0.000 abstract description 8
- 229940088710 antibiotic agent Drugs 0.000 description 26
- YXQXDXAHCSEVSD-GCYNEOGWSA-N dynamutilin Chemical compound OC(=O)\C=C\C(O)=O.CCN(CC)CCSCC(=O)O[C@@H]1C[C@@](C)(C=C)[C@@H](O)[C@H](C)[C@@]23CC[C@@H](C)[C@]1(C)[C@@H]2C(=O)CC3 YXQXDXAHCSEVSD-GCYNEOGWSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- ONXOKWFYBIQOFQ-VSXSCALHSA-N ac1l4s0d Chemical compound OS(O)(=O)=O.O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O.O[C@@H]1[C@H](O)[C@@H](O)[C@@H](SC)O[C@@H]1[C@@H]([C@@H](C)O)NC(=O)[C@H]1N(C)C[C@H](C(C)C)C1 ONXOKWFYBIQOFQ-VSXSCALHSA-N 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 229960000268 spectinomycin Drugs 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 6
- 229960004885 tiamulin Drugs 0.000 description 6
- UURAUHCOJAIIRQ-QGLSALSOSA-N tiamulin Chemical compound CCN(CC)CCSCC(=O)O[C@@H]1C[C@@](C)(C=C)[C@@H](O)[C@H](C)[C@@]23CC[C@@H](C)[C@]1(C)[C@@H]2C(=O)CC3 UURAUHCOJAIIRQ-QGLSALSOSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- XGBFWQUQYQIFLB-MTTMTQIXSA-N 23312-56-3 Chemical compound OS(O)(=O)=O.O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O XGBFWQUQYQIFLB-MTTMTQIXSA-N 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 241001430197 Mollicutes Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 241000204045 Mycoplasma hyopneumoniae Species 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 229960002227 clindamycin Drugs 0.000 description 2
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- LKKVGKXCMYHKSL-LLZRLKDCSA-N gentamycin A Chemical compound O[C@H]1[C@H](NC)[C@@H](O)CO[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)[C@@H](N)C[C@H]1N LKKVGKXCMYHKSL-LLZRLKDCSA-N 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- BUFQZEHPOKLSTP-UHFFFAOYSA-M sodium;oxido hydrogen sulfate Chemical compound [Na+].OS(=O)(=O)O[O-] BUFQZEHPOKLSTP-UHFFFAOYSA-M 0.000 description 2
- -1 sulfate salt Chemical class 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000589893 Brachyspira hyodysenteriae Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 208000003495 Coccidiosis Diseases 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010017964 Gastrointestinal infection Diseases 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 206010023076 Isosporiasis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000970875 Streptomyces spectabilis Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000003377 anti-microbal effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- CEAZRRDELHUEMR-UHFFFAOYSA-N gentamicin Chemical class O1C(C(C)NC)CCC(N)C1OC1C(O)C(OC2C(C(NC)C(C)(O)CO2)O)C(N)CC1N CEAZRRDELHUEMR-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- QZIQJVCYUQZDIR-UHFFFAOYSA-N mechlorethamine hydrochloride Chemical compound Cl.ClCCN(C)CCCl QZIQJVCYUQZDIR-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/195—Antibiotics
Definitions
- the present application is a Patent of Addition to the Slovenian Patent Application P-9200002 and relates to a veterinary composition as an additive to drinking water or animal feed, which contains an antibiotic mixture of gentamicin and lincomycin, both being also in the form of free bases or acid addition salts such as gentamicin sulfate and lincomycin hydrochloride, for use in the prophylaxis of colibacilliosis and enzootic pneumonia and therapy of dysentery of pigs and, consequently, for increasing the gain In their body weight, reducing the losses, reducing the number of poorly developed animals and improving the utilization of feed (conversion).
- an antibiotic mixture of gentamicin and lincomycin both being also in the form of free bases or acid addition salts such as gentamicin sulfate and lincomycin hydrochloride
- Lincomycin is a known antibiotic described in US patent 3,086,912, which inhibits the growth and propagation of numerous microorganisms, particularly of gram-positive bacteria such as species Staphylococcus, Streptococcus, Clostridium, Bacillus anthracis and Corybacterium, of some gram-negative bacteria, such as Bordetella and Haemophilus, of some species Nocardia, and of Actinomyces.
- Gentamicin is an antibiotic described in US Patents 3,091,572 and 3,136,704 and it consists of three structurally related components, gentamicins C 1 , C 2 and C 1a . Well-known is also gentamicin A, whose structure differs from other components of the complex. In galenic forms gentamicin occurs in the form of C complex sulfate (gentamicin sulfate). Gentamicin is a very effective antibiotic against gram-positive and gram-negative microorganisms such as species Staphylococcus, Pneunomonas and Proteus and is used in both human and veterinary medicine.
- Spectinomycin is an antibiotic isolated from the fermentation broth of Streptomyces spectabilis and is described in US Patent 3,234,094. Spectinomycin is active against Mycoplasma, some gram-positive and most of gram-negative bacteria and is used in veterinary medicine. In US Patent 3,245,497 there is described an animal feed containing spectinomycin in an amount effective for speeding up the growth of fattening animals.
- EP-A-0 026 746 describes a pharmaceutical preparation and a process for increasing the antibiotic efficiency of antibiotics, which are based on the combination of one or more antibiotics and muramylpeptide of the formula I. Particularly muramylpeptides of the formula II can be used.
- gentamicin as an aminoglycosidic antibiotic and lincomycin or clindamycin as a lincomycinic antibiotic can be used.
- the examples demonstrate the use of only one antibiotic in the combination with muramylpeptides and necessarily muramylpeptides must always be used in combination with an antibiotic.
- GB-A-2 159 409 describes a synergistic antibiotic combination useful for the treatment of respiratory, gastrointestinal as well as urinary infections and septicaemia of domestic animals, comprising tiamulin hydrogen fumarate and an aminoglycosidic antibiotic such as gentamicin or pharmaceutically acceptable salts thereof in a mass ratio of from 1:5 to 5:1.
- Example 5 shows a combination of tiamulin and gentamicin in a mass ratio of 4:1.
- the lincomycin antibiotics used in addition to gentamicin in the present application are structurally entirely different from tiamulin.
- WO-A-8 500 515 describes inter alia the antimicrobial agents gentamycin and clindamycin coencapsulated in one liposome preparation for the treatment of anaerobic infections, wherein this liposome preparation is applied intraperitoneal.
- Tiamulin a semisynthetic antibiotic with a broad spectrum of antimicrobic activity, is described in US Patent 3,919,290 and especially acts on Mycoplasmas but also on a number of gram-positive and gram-negative bacteria.
- it is used in the prophylaxis and therapy of bloody dysentery and enzootic pneumonia in pigs as well as of other infections caused by microorganisms sensitive to tiamulin (in the form of hydrogen fumarate). It is also used in the prophylaxis and therapy of animal respiratory diseases caused by mycoplasmas and secondary infections.
- the present invention is based on the task to find an efficient combination of antibiotics in the composition of a veterinary formulation as an additive to drinking water and animal feed for use in the prophylaxis of colibacilliosis and enzootic pneumonia and therapy of dysentery and, consequently, for increasing the gain in their body weight, reducing the losses as well as reducing the number of poorly developed animals and their death rate.
- the results obtained by such a combination of antibiotics In the composition of the veterinary formulation as an additive to drinking water or animal feed should be superior to the action of individual antibiotics or of well-known combinations of antibiotics for the same purposes, thus representing a valuable improvement in pig breeding.
- Gastrointestinal diseases are primarily caused by E. coli, which causes disturbances in the intestinal tract of a newborn piglet and also at older age, especially after weaning.
- E. coli is a natural inhabitant of the digestive tract as a saprophyte together with many other bacteria, whereat at changed conditions in organism some strains of E.coli cause a disease.
- coliinfection of pigs is to be understood as a complex of gastrointestinal diseases of diarrhoeatical character. Three forms of diseases, which are connected to the age of piglets, can be distinguished: colidiarrhoea of newborn pigs from the seventh day, colibacilliosis of sucking pigs older than ten days, and coligastroenteritis and colienterotoxemy of weanling pigs.
- enzootic mycoplasmotic pneumonia Another disease causing considerable direct and indirect losses (deaths and deaths as a result of poor development of pigs as a result of the disease) in intensive pig breeding is enzootic mycoplasmotic pneumonia.
- This disease is primarily caused by Mycoplasma hyopneumoniae. In worsened microclimatic conditions, in cooperation with some bacteria, it causes a chronic disease of high morbidity and low lethality (death). In pigs of the age of 3 to 8 weeks the disease runs acutely and in bad microclimatic conditions the lethality can be higher than 10 %. The death appears mainly because of secondary bacterial infections.
- a pig with enzootic pneumonia has smaller gain in weight and a smaller conversion.
- the composition of the present invention includes lincomycin and gentamicin, possibly in the form of free bases and preferably in the form of their pharmaceutically acceptable acid addition salts such as lincomycin hydrochloride and gentamicin sulfate, in parts by weight from 1:1 to 1:10, in addition to the usual water-soluble basis. The best results are achieved with the ratio of lincomycin hydrochloride : gentamicin sulfate from 1:1 to 1:3.
- the composition of the present invention can be added to drinking water or usual animal feed.
- composition is administered from the first day of weaning on.
- composition of the present invention was clinically tested on pigs in comparison with the commercial composition Linco-Spectin® 44 Premix containing equal parts of lincomycin hydrochloride and spectinomycin sulfate, and with the commercial composition Tiavet® P 2 % powder containing tiamulin hydrogen fumarate, which can be both added to drinking water or to usual pig feed in accordance with the producer's recommendations.
- composition of the present invention can be administered for prophylaxis of colibacilliosis and enzootic pneumonia and therapy of dysenthery in pigs and therefore for increasing the gain in their body weight.
- the combination of both antibiotics is added in a concentration from 1 mg/ml to 200 mg/ml of drinking water, yet the best results are obtained with a concentration of both antibiotics of about 50 mg/ml drinking water.
- the combination of both antibiotics is added to animal feed for pigs in a total concentration from 0.5 kg/t to 5 kg/t, preferably about 1.5 kg/t of solid food.
- a comparative testing of the above-named antibiotics or combinations of antibiotics was carried out in order to clinically test the efficiency of the combination of antibiotics of the present invention for the prophylaxis of colibacilliosis and enzootic pneumonia in pigs and thus to establish the gain in body weight.
- antibiotics of the present invention was prepared in the form of a powdery composition with following ingredients: lincomycin hydrochloride 1.5 g gentamicin sulfate 4.0 g polyethylene glycol 4000 powder 2.0 g lactose 42.5 g 50.0g
- the composition was prepared by mixing fine-grained solid ingredients in a mixer, and could then he added to drinking water or animal feed.
- the combination of antibiotics lincomycin-spectinomycin was applied in the form of the commercial composition Linco-Spectin® 44 Premix (Upjohn Comp., USA) containing lincomycin hydrochloride and spectinomycin sulfate in a ratio of 1:1, whereas tiamulin was applied in the form of the commercial composition Tiavet® P 2% powder (Pliva, Croatia) containing tiamulin hydrogen fumarate.
- composition of the present invention was added to drinking water in a dose of 50 g to 100 l of water from the first to 21st day after weaning.
- the building was washed with hot water under pressure and disinfected with the composition Virkon® (Krka, Slovenia), which is an equilibrated and stabilized mixture of peroxide compounds, surfactants, organic acids and an organic buffer system.
- the main ingredient is potassium peroxisulfate (50%).
- the piglets received the vitamin composition BCK-forte+E powder (Alkaloid, Skopje, LORDia) containing vitamins A, B 3 , E, C, B 1 , B 2 , B 6 and B 12 in drinking water in a dose of 200 g to 100 l of water for 2 days.
- BCK-forte+E powder Alkaloid, Skopje, LORDia
- composition of the present invention in drinking water in a dose of 50 g to 100 l of water.
- the piglets in parallel testing were also receiving the vitamin composition BCK-forte+E in drinking water in a dose of 200 g to 100 l of water for 2 days.
- the pigs were weighed at weaning and at moving to the fattening place (Tables 2 and 3).
- Table 2 shows that the group of piglets receiving the composition of the present invention in drinking water reached the biggest average body weight and the biggest daily gain by the time of moving to the fattening place.
- Total losses and deaths with symptoms of diarrhoea or pneumonia, and conversion of feed during breeding period Composition Number of animals Losses (%) Deaths Conversion Diarrhoea (%) Pneumonia (%) of this invention 1620 4.75 3.45 1.30 2.16 Linco-Spectin® 44 premix 1687 7.05 5.10 1.95 2.22 Tiavet® P 2% 1602 9.42 6.05 3.37 2.38
- Table 3 shows that in the group receiving the composition of the present invention, the total losses and deaths with symptoms of diarrhoea and pneumonia during the breeding time were the lowest in comparison with the groups in parallel testing.
- the conversion is the lowest in the group receiving the composition of the present invention.
- Number of poorly developed piglets and share of their deaths Composition Poorly developed animals Deaths number (%) number (%) of this invention 26 1.6 / / Linco-Spectin® 44 premix 89 5.28 27 30.3 Tiavet® P 2% 112 6.99 38 33.9
- Table 4 shows that the group receiving the composition of the present invention has the lowest percentage of poorly developed piglets and that none of them died in this group, whereas in the comparative group more than 30% of them died.
- composition of the present invention in weanling pigs showed that the composition does not have any side effects.
- the group of weanling pigs receiving the composition of the present invention showed better results in comparison with comparative groups receiving the commercial compositions Linco-Spectin® 44 premix and Tiavet® P 2% with regard to:
- the percentage composition of animal feed for pigs to which the combination of the present invention is added can be made up of following ingredients:
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Abstract
Described is new veterinary preparation, which is added to drinking water or to animal feed for pigs and contains 1 part by weight of lincomycin and 1 to 10 parts by weight of gentamicin or their pharmaceutically acceptable acid addition salts in a usual carrier for the use in the prophylaxis and therapy of dysentery and colibacilliosis and in the prophylaxis of enzootic pneumonia of pigs and hence for increasing the gain in their body weight. The new veterinary preparation for pig breeding has shown improved characteristics reflecting in a reduction of total losses and deaths with symptoms of diarrhoea and pneumonia, in a decrease of the percentage of poorly developed pigs and in the absence of their deaths, in a decrease of the conversion, and in an improvement of the average daily gain in the body weight.
Description
The present application is a Patent of Addition to the Slovenian Patent Application
P-9200002 and relates to a veterinary composition as an additive to drinking water
or animal feed, which contains an antibiotic mixture of gentamicin and lincomycin,
both being also in the form of free bases or acid addition salts such as gentamicin sulfate
and lincomycin hydrochloride, for use in the prophylaxis of
colibacilliosis and enzootic pneumonia and therapy of dysentery of pigs and, consequently,
for increasing the gain In their body weight, reducing the losses, reducing
the number of poorly developed animals and improving the utilization of feed
(conversion).
In intensive pig breeding the biggest losses in weanling pigs are caused by gastrointestinal
and pneumonic diseases, therefore a constant need exists for an efficient
prophylaxis and therapy of these infections with efficient antibiotics or combinations
thereof as additives to drinking water or animal feed, whereby also the gain in body
weight would be increased and mortality of piglets would be reduced.
From the literature the use of different antibiotics and combinations of antibiotics is
known, which are added to animal feed and drinking water for prophylaxis and treatment
of fattening animals and which at the same time act on the gain in body weight.
Lincomycin is a known antibiotic described in US patent 3,086,912, which inhibits the
growth and propagation of numerous microorganisms, particularly of gram-positive
bacteria such as species Staphylococcus, Streptococcus, Clostridium, Bacillus
anthracis and Corybacterium, of some gram-negative bacteria, such as Bordetella
and Haemophilus, of some species Nocardia, and of Actinomyces. It is specially effective
against Treponema hyodysenteriae, Mycoplasma hyopneumoniae and Mysoplasma
galliseticum. Upon sensitive microorganisms it acts bacteriostatically, at
higher concentrations (2 to 3 fold MIC value) also bactericidally.
In US patent 3,155,580, there are described galenic forms on the basis of lincomycin
and of its acid addition salts as the active ingredient for the treatment of infections in
humans and animals caused by bacteria. In fattening animals the antibiotic can be
used prophylactically and for the increase in the gain in body weight.
From US Patent 3,150,042 the use of lincomycin for prophylactic and therapeutical
treatment of coccidiosis in animals is known, whereat the antibiotic is used as an additive
to usual animal feed or to an appropriate amount of drinking water. There is
also described the administration of tablets and sterile injection solutions.
Gentamicin is an antibiotic described in US Patents 3,091,572 and 3,136,704 and it
consists of three structurally related components, gentamicins C1, C2 and C1a. Well-known
is also gentamicin A, whose structure differs from other components of the
complex. In galenic forms gentamicin occurs in the form of C complex sulfate
(gentamicin sulfate). Gentamicin is a very effective antibiotic against gram-positive
and gram-negative microorganisms such as species Staphylococcus, Pneunomonas
and Proteus and is used in both human and veterinary medicine.
Spectinomycin is an antibiotic isolated from the fermentation broth of Streptomyces
spectabilis and is described in US Patent 3,234,094. Spectinomycin is active against
Mycoplasma, some gram-positive and most of gram-negative bacteria and is used in
veterinary medicine. In US Patent 3,245,497 there is described an animal feed containing
spectinomycin in an amount effective for speeding up the growth of fattening
animals.
EP-A-0 026 746 describes a pharmaceutical preparation and a process for increasing
the antibiotic efficiency of antibiotics, which are based on the combination
of one or more antibiotics and muramylpeptide of the formula I. Particularly
muramylpeptides of the formula II can be used. Among the numerous cited possible
antibiotics, gentamicin as an aminoglycosidic antibiotic and lincomycin or
clindamycin as a lincomycinic antibiotic can be used. The examples demonstrate
the use of only one antibiotic in the combination with muramylpeptides and
necessarily muramylpeptides must always be used in combination with an antibiotic.
GB-A-2 159 409 describes a synergistic antibiotic combination useful for the
treatment of respiratory, gastrointestinal as well as urinary infections and septicaemia
of domestic animals, comprising tiamulin hydrogen fumarate and an aminoglycosidic
antibiotic such as gentamicin or pharmaceutically acceptable salts thereof
in a mass ratio of from 1:5 to 5:1. Example 5 shows a combination of tiamulin and
gentamicin in a mass ratio of 4:1. The lincomycin antibiotics used in addition to
gentamicin in the present application are structurally entirely different from tiamulin.
WO-A-8 500 515 describes inter alia the antimicrobial agents gentamycin and
clindamycin coencapsulated in one liposome preparation for the treatment of
anaerobic infections, wherein this liposome preparation is applied intraperitoneal.
In US Patent 3,261,687 there is described an animal feed containing a combination of
antibiotics spectinomycin (in the form of sulfate salt) and lincomycin (in the form of
hydrochloride salt) and a method for increasing the gain in the body weight in fattening
animals, where the ratio of antibiotics in the animal feed composition or in drinking
water is from 1 to 10 parts by weight of spectinomycin and 1 part by weight of
lincomycin. It is reported that with such a combination of antibiotics in animal feed
or drinking water unexpectedly good results in the increase in the gain in the body
weight and its adding rate are achieved. A combination of both antibiotics In the
animal feed acts synergistically and is also suitable for therapeutic and prophylactic
treatment of infections in animals to be fattened.
Further, from US Patent 3,679,787 there is known a combination of lincomycin and
spectinomycin in a dosage unit, in a combination with carriers, which is suitable for
treating animal diseases because of the synergistic activity of the combination against
infections by Mycoplasma.
Tiamulin, a semisynthetic antibiotic with a broad spectrum of antimicrobic activity, is
described in US Patent 3,919,290 and especially acts on Mycoplasmas but also on a
number of gram-positive and gram-negative bacteria. In the veterinary medicine it is
used in the prophylaxis and therapy of bloody dysentery and enzootic pneumonia in
pigs as well as of other infections caused by microorganisms sensitive to tiamulin (in
the form of hydrogen fumarate). It is also used in the prophylaxis and therapy of
animal respiratory diseases caused by mycoplasmas and secondary infections.
The present invention is based on the task to find an efficient combination of antibiotics
in the composition of a veterinary formulation as an additive to drinking water
and animal feed for use in the prophylaxis of colibacilliosis and enzootic pneumonia
and therapy of dysentery and, consequently, for increasing the gain in their body
weight, reducing the losses as well as reducing the number of poorly developed
animals and their death rate. The results obtained by such a combination of antibiotics
In the composition of the veterinary formulation as an additive to drinking
water or animal feed should be superior to the action of individual antibiotics or of
well-known combinations of antibiotics for the same purposes, thus representing a
valuable improvement in pig breeding.
In the Slovenian Patent Application P-9200002 there is described an animal feed and
an additive to animal feed or to drinking water in poultry breeding, which contains a
mixture of antibiotics of 1 part by weight of gentamicin sulfate and 5 to 60 parts by
weight of lincomycin hydrochloride, for prophylaxis and therapy of infections and
thus for increasing the gain in their body weight, whereby the efficiency factor was increased
at low feed conversion and the total death rate was reduced.
In intensive pig breeding, the biggest losses in weanling pigs, i.e. in pigs after they
have stopped sucking at the age of about three weeks, are caused by gastrointestinal
and pneumonic diseases. Gastrointestinal diseases are primarily caused by E. coli,
which causes disturbances in the intestinal tract of a newborn piglet and also at older
age, especially after weaning. E. coli is a natural inhabitant of the digestive tract as a
saprophyte together with many other bacteria, whereat at changed conditions in organism
some strains of E.coli cause a disease.
Pathological states in animals are provoked only by those variants of E.coli that are
able to produce enterotoxins. The term coliinfection of pigs is to be understood as a
complex of gastrointestinal diseases of diarrhoeatical character. Three forms of diseases,
which are connected to the age of piglets, can be distinguished: colidiarrhoea
of newborn pigs from the seventh day, colibacilliosis of sucking pigs older than ten
days, and coligastroenteritis and colienterotoxemy of weanling pigs.
Another disease causing considerable direct and indirect losses (deaths and deaths as
a result of poor development of pigs as a result of the disease) in intensive pig breeding
is enzootic mycoplasmotic pneumonia. This disease is primarily caused by
Mycoplasma hyopneumoniae. In worsened microclimatic conditions, in cooperation
with some bacteria, it causes a chronic disease of high morbidity and low lethality
(death). In pigs of the age of 3 to 8 weeks the disease runs acutely and in bad
microclimatic conditions the lethality can be higher than 10 %. The death appears
mainly because of secondary bacterial infections. A pig with enzootic pneumonia has
smaller gain in weight and a smaller conversion.
In our research regarding the possibilities of preventing coliinfections and enzootic
pneumonia of weanling pigs, it was surprisingly found that by adding the novel composition
of the present invention to drinking water or usual pig feed the desired aim
is achieved and its efficiency regarding the prophylactic and therapeutic characteristics
is superior to that of some well-known commercial compositions for the same
purpose.
The composition of the present invention includes lincomycin and gentamicin, possibly
in the form of free bases and preferably in the form of their pharmaceutically
acceptable acid addition salts such as lincomycin hydrochloride and gentamicin sulfate,
in parts by weight from 1:1 to 1:10, in addition to the usual water-soluble basis.
The best results are achieved with the ratio of lincomycin hydrochloride : gentamicin
sulfate from 1:1 to 1:3. The composition of the present invention can be added to
drinking water or usual animal feed.
The composition is administered from the first day of weaning on.
The composition of the present invention was clinically tested on pigs in comparison
with the commercial composition Linco-Spectin® 44 Premix containing equal parts
of lincomycin hydrochloride and spectinomycin sulfate, and with the commercial
composition Tiavet® P 2 % powder containing tiamulin hydrogen fumarate, which
can be both added to drinking water or to usual pig feed in accordance with the
producer's recommendations.
The obtained results of comparative clinical testings on pigs demonstrated - which is
also illustrated in the Examples - that an application of the composition of the
present invention, in comparison with commercial compositions, reduces the total
losses and deaths with symptoms of dysentery and pneumonia during breeding,
reduces the percentage of poorly developed pigs with no deaths occurring among
them and, additionally, the conversion (use of food) is the lowest at applying the
composition of the present invention, therefore the average daily gain in body weight
is improved.
On the basis of the obtained results, the composition of the present invention can be
administered for prophylaxis of colibacilliosis and enzootic pneumonia and therapy
of dysenthery in pigs and therefore for increasing the gain in their body weight.
The combination of both antibiotics is added in a concentration from 1 mg/ml to
200 mg/ml of drinking water, yet the best results are obtained with a concentration of
both antibiotics of about 50 mg/ml drinking water.
The combination of both antibiotics is added to animal feed for pigs in a total concentration
from 0.5 kg/t to 5 kg/t, preferably about 1.5 kg/t of solid food.
The invention is illustrated, yet not limited by the following Examples:
Comparative clinical testing of a combination of the antibiotics of the present invention
(lincomycin-gentamicin), of a combination lincomycin-spectinomycin and of
tiamulin in pigs
A comparative testing of the above-named antibiotics or combinations of antibiotics
was carried out in order to clinically test the efficiency of the combination of antibiotics
of the present invention for the prophylaxis of colibacilliosis and enzootic
pneumonia in pigs and thus to establish the gain in body weight.
The combination of antibiotics of the present invention was prepared in the form of a
powdery composition with following ingredients:
| lincomycin hydrochloride | 1.5 g |
| gentamicin sulfate | 4.0 g |
| polyethylene glycol 4000 powder | 2.0 g |
| lactose | 42.5 g |
| 50.0g |
The composition was prepared by mixing fine-grained solid ingredients in a mixer,
and could then he added to drinking water or animal feed.
The combination of antibiotics lincomycin-spectinomycin was applied in the form of
the commercial composition Linco-Spectin® 44 Premix (Upjohn Comp., USA) containing
lincomycin hydrochloride and spectinomycin sulfate in a ratio of 1:1, whereas
tiamulin was applied in the form of the commercial composition Tiavet® P 2% powder
(Pliva, Croatia) containing tiamulin hydrogen fumarate.
In the clinical testing of the composition of the present invention three groups of
weanling pigs were included:
- a group of 1620 weanling pigs receiving the composition of the present invention,
- a group of 1687 weanling pigs receiving the composition Linco-Spectin® 44 premix,
- a group of 1602 weanling pigs receiving the composition Tiavet® P 2% powder.
Piglets of all three groups were of the same genetic origin.
The composition of the present invention was added to drinking water in a dose of
50 g to 100 l of water from the first to 21st day after weaning.
In animals receiving the composition of the present invention in drinking water no
side effects were observed.
Before settling the test animals, the building was washed with hot water under pressure
and disinfected with the composition Virkon® (Krka, Slovenia), which is an
equilibrated and stabilized mixture of peroxide compounds, surfactants, organic acids
and an organic buffer system. The main ingredient is potassium peroxisulfate (50%).
Immediately after settling, the piglets received the vitamin composition BCK-forte+E
powder (Alkaloid, Skopje, Macedonia) containing vitamins A, B3, E, C, B1,
B2, B6 and B12 in drinking water in a dose of 200 g to 100 l of water for 2 days.
From the first to 21st day after weaning the piglets received the composition of the
present invention in drinking water in a dose of 50 g to 100 l of water.
In tested piglets the appearance of diarrhoea and pneumonia as well as deaths were
monitored daily. The pigs were weighed at weaning and at moving to the fattening
place (Tables 2 and 3).
The results of tests at which the composition of the present invention was used are
shown in Tables 2, 3, 4, and 5.
During the period of clinical testing of the composition of the present invention, 26
piglets (1.6%) falling behind in the gain in the body weight were separated in two
separate boxes. By the time of moving into the fattening place, none of these pigs had
died.
During the breeding period, 3.45% of piglets with diarrhoea symptoms and 1.3% of
piglets with pneumonia symptoms died (Table 3).
Simultaneously two groups of pigs were tested in same age period and in equal sties.
Before settling the piglets, both buildings were washed with hot water and then disinfected
with the composition Virkon® (Krka, Slovenia).
In the first comparative group there were 1687 weanling pigs receiving the product
Linco-Spectin® 44 premix in the feed, in accordance with the producer's recommendations,
in a dose of 1 kg to 1 tonne of feed for 21 days.
Due to the technological process of the farm, the medicine was administered to the
piglets beginning with the eighth day after weaning.
In the second comparative group, there were 1602 weaning pigs receiving the composition
Tiavet® P 2% powder in the feed, in accordance with the producer's recommendations,
in a dose of 1.25 g to 1 tonne of feed for 21 days (Table 1). Also to this
group the composition was administered beginning with the eighth day after weaning.
In addition to the above-mentioned antibiotics in feed, the piglets in parallel testing
were also receiving the vitamin composition BCK-forte+E in drinking water in a
dose of 200 g to 100 l of water for 2 days.
In the animals in parallel testing, the appearance of diarrhoea and pneumonia as well
as deaths were monitored daily.
The pigs were weighed at weaning and at moving to the fattening place (Tables 2 and
3).
During the period of clinical testing, 89 poorly developed piglets (5.28%) were
separated from the group receiving Linco-Spectin® 44 premix, and 27 of them died
(30.3 %). From the group receiving Tiavet® P 2% powder, 112 piglets (6.9 %) falling
behind in the gain in the body weight were separated and 38 of them died (33.9%).
| Number of animals in groups, the product and administration | |||
| Composition | Number of animals | Dose | Administ.time (days) |
| of this invention | 1620 | 50 g/100 l of water | 21 |
| Linco-Spectin® 44 premix | 1687 | 1 kg/1 t of feed | 21 |
| Tiavet® P 2% | 1602 | 1.25 kg/1 t of feed | 21 |
| Average body weight of piglets at weaning, at removing to fattening place and average daily gain | |||
| Composition | Body weight at weaning | Body weight at moving | Average daily gain of the body weight |
| of this invention | 7.32 kg | 30.17 kg | 375 g |
| Linco-Spectin® 44 premix | 7.11 kg | 27.91 kg | 346 g |
| Tiavet® P 2% | 7.20 kg | 28.31 kg | 329 g |
Table 2 shows that the group of piglets receiving the composition of the present invention
in drinking water reached the biggest average body weight and the biggest
daily gain by the time of moving to the fattening place.
| Total losses and deaths with symptoms of diarrhoea or pneumonia, and conversion of feed during breeding period | |||||
| Composition | Number of animals | Losses (%) | Deaths | Conversion | |
| Diarrhoea (%) | Pneumonia (%) | ||||
| of this invention | 1620 | 4.75 | 3.45 | 1.30 | 2.16 |
| Linco-Spectin® 44 premix | 1687 | 7.05 | 5.10 | 1.95 | 2.22 |
| Tiavet® P 2% | 1602 | 9.42 | 6.05 | 3.37 | 2.38 |
Table 3 shows that in the group receiving the composition of the present invention,
the total losses and deaths with symptoms of diarrhoea and pneumonia during the
breeding time were the lowest in comparison with the groups in parallel testing.
The conversion is the lowest in the group receiving the composition of the present
invention.
| Number of poorly developed piglets and share of their deaths | ||||
| Composition | Poorly developed animals | Deaths | ||
| number | (%) | number | (%) | |
| of this invention | 26 | 1.6 | / | / |
| Linco-Spectin® 44 premix | 89 | 5.28 | 27 | 30.3 |
| Tiavet® P 2% | 112 | 6.99 | 38 | 33.9 |
Table 4 shows that the group receiving the composition of the present invention has
the lowest percentage of poorly developed piglets and that none of them died in this
group, whereas in the comparative group more than 30% of them died.
In Table 5, the total results of all groups receiving the composition of the present invention,
Linco-Spectin® 44 premix and Tiavet® P 2% are shown.
A summary of the results of clinical testing of the composition of the present invention:
Clinical testing of the composition of the present invention in weanling pigs showed
that the composition does not have any side effects.
The group of weanling pigs receiving the composition of the present invention
showed better results in comparison with comparative groups receiving the commercial
compositions Linco-Spectin® 44 premix and Tiavet® P 2% with regard to:
- average daily gain,
- average feed conversion,
- percentage of total losses,
- percentage of dead piglets with pneumonia symptoms,
- percentage of dead piglets with diarrhoea symptoms,
- percentage of poorly developed piglets
- percentage of poorly developed piglets that died.
| Results of testing with the composition | composition of this invention | LINCO-SPECTIN® 44 premix | TIAVET® P 2% | |
| active amount | gentamicin sulfate + lincomycin.HCl | Lincomycin.HCl spectinomycin sulfate | Tiamulin hydrogen fumarate | |
| Number of weanling pigs | 1620 | 1687 | 1602 | |
| Total weight of weanling pigs | kg | 11858.40 | 11994.57 | 11534.40 |
| Average age of weanling pigs | days | 30.22 | 29.55 | 29.37 |
| Average weight of weanling pigs | kg | 7.32 | 7.11 | 7.20 |
| Administration of medicines | days | 21 | 21 | 21 |
| Breeding period | days | 63 | 65 | 66 |
| Average weight at the end | kg | 30.17 | 27.91 | 28.31 |
| Average daily gain | g | 375 | 346 | 329 |
| Average feed conversion | kg | 2.16 | 2.22 | 2.38 |
| Feed consumption/fattening day | kg | 0.81 | 0.77 | 0.79 |
| Number of weanling pigs | 1620 | 1687 | 1602 | |
| Losses | number of animals | 77 | 119 | 151 |
| Losses | % | 4.75 | 7.05 | 9.43 |
| Number of dead piglets - diarrhoea | 56 | 86 | 97 | |
| Number of dead piglets - pneumonia | 21 | 33 | 54 |
The percentage composition of animal feed for pigs to which the combination of the
present invention is added can be made up of following ingredients:
Claims (3)
- A veterinary composition as an additive to drinking water or to animal feed for pigs, characterised in that it contains an antibiotic mixture of 1 part by weight of lincomycin and 1 to 10 parts by weight of gentamicin or their pharmaceutically acceptable acid addition salts with a water-soluble carrier.
- A veterinary composition as an additive to drinking water or to animal feed for pigs according to claim 1, characterised in that it contains an antibiotic mixture of 1 part by weight of lincomycin hydrochloride and 1 to 3 parts by weight of gentamicin sulfate.
- A veterinary compositon as an additive to drinking water or to animal feed for pigs according to claims 1 or 2 for use in the prophylaxis of colibacilliosis and enzootic pneumonia and therapy of dysentery and hence for increasing the gain in their body weight and to improve the feed utilization in pigs.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI16792 | 1992-08-11 | ||
| SI9216007 | 1992-11-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0597167A1 EP0597167A1 (en) | 1994-05-18 |
| EP0597167B1 true EP0597167B1 (en) | 1998-10-14 |
Family
ID=20431077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP93100071A Expired - Lifetime EP0597167B1 (en) | 1992-08-11 | 1993-01-05 | Veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0597167B1 (en) |
| AT (1) | ATE172077T1 (en) |
| CA (1) | CA2086949A1 (en) |
| DE (1) | DE69321554T2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1314359A1 (en) * | 2001-11-21 | 2003-05-28 | N.V. Seghers Nutrition Sciences | Growth promoter composition for animals |
| HU229104B1 (en) | 2007-11-22 | 2013-07-29 | Pharmateka Bt | Use of edta and its salts for the prevention and treatment of bacterial intestinal swine diseases caused by brachyspira hyodysenteriae and for enhancement of efficiency of antibiotics in curing such illnesses |
| HU230466B1 (en) | 2012-08-30 | 2016-07-28 | PHARMATÉKA Kutató, Fejlesztő és Szolgáltató Kft. | Use of an anti-germ preventive composition comprising methylglyoxal or methylglyoxal diacetate and organic acids and/or na salts thereof for poultry bedding disinfection |
| CN114748495B (en) * | 2022-05-18 | 2023-02-03 | 广东温氏大华农生物科技有限公司 | Oil-water double-soluble veterinary linke grand compound preparation and preparation method and application thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3261687A (en) * | 1964-09-21 | 1966-07-19 | Upjohn Co | Animal feed containing lincomycin and spectinomycin |
| EP0026746B1 (en) * | 1979-10-02 | 1985-04-10 | Ciba-Geigy Ag | Combinatory compositions for use in a method for enhancing the activity of antibiotics, antibiotic preparations having enhanced activity and process for their production |
| NZ195903A (en) * | 1979-12-26 | 1983-05-31 | Lilly Co Eli | Macrolide and aminoglycoside antibiotic composition |
| BE902010A (en) * | 1984-03-28 | 1985-09-25 | Hajdusagi Agraripari Egyesules | NOVEL SYNERGISTIC DRUG COMBINATIONS AND PROCESS FOR PREPARING THE SAME. |
-
1993
- 1993-01-05 DE DE69321554T patent/DE69321554T2/en not_active Expired - Fee Related
- 1993-01-05 EP EP93100071A patent/EP0597167B1/en not_active Expired - Lifetime
- 1993-01-05 AT AT93100071T patent/ATE172077T1/en not_active IP Right Cessation
- 1993-01-08 CA CA002086949A patent/CA2086949A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE69321554D1 (en) | 1998-11-19 |
| ATE172077T1 (en) | 1998-10-15 |
| CA2086949A1 (en) | 1994-02-12 |
| DE69321554T2 (en) | 1999-06-24 |
| EP0597167A1 (en) | 1994-05-18 |
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